Medicament delivery and packaging

ABSTRACT

A system is disclosed for the administration of a powdered medicament by inhalation. The system comprises a container ( 20, 60, 120 ) containing a unit dose of medicament in powder form, the container ( 20, 60, 120 ) having at least one dispensing aperture ( 21 ), and a device ( 10, 50, 100 ) having a chamber ( 19, 56, 110 ) adapted to receive said container ( 20, 60, 120 ). The device ( 10, 50, 100 ) further comprises air inlet means ( 12, 12   a   , 13, 13   a   , 112, 113 ) by which air may be drawn into the chamber ( 19, 56, 110 ) and means ( 11, 111 ) by which air and entrained medicament may be drawn out of the chamber ( 19, 56, 110 ). The system is arranged such that the container ( 20, 60, 120 ), in use, is stationary within the chamber ( 19, 56, 110 ).

This invention relates to delivery devices and packaging formedicaments, in particular to delivery devices and packaging for theadministration of medicaments by inhalation.

The most common methods of administering powdered medicament byinhalation are pressurised aerosol inhalers and dry powder inhalers.Conventional dry powder inhalers use medicament packaged in a gelatinecapsule. An improved method of administration, however, is disclosed inWO 98/26828.

WO 98/26828 discloses several delivery devices for use with medicamentcontainers that contain pre-formed openings through which medicament isdispensed within the delivery device. The delivery devices all comprisea mouthpiece, air inlet means and a chamber in which the medicamentcontainer is located. In use, air is drawn into the chamber causing themedicament container to follow an orbital path around the chamber. Inthis way the medicament is dispensed through the openings of themedicament container and medicament entrained with air is drawn out ofthe chamber and through the mouthpiece. The disclosed delivery devicesinclude single-use delivery devices pre-loaded with a medicamentcontainer and multi-use delivery devices in which a medicament containeris inserted into the chamber before use.

The delivery devices and medicament packages disclosed in WO 98/26828represent a considerable advance over the prior art, but are nonethelesssusceptible to further improvement. In particular, the movement of themedicament container may, in use, be audible, which may be undesirablein certain situations.

There has now been devised an improved form of medicament deliverydevice and medicament packaging that overcomes or substantiallymitigates the above-mentioned and/or other disadvantages of the priorart. In particular, it has surprisingly been found that a medicamentcontainer of the general type disclosed in WO 98/26828 may be caused toempty satisfactorily without undergoing movement.

According to the invention, there is provided a system for theadministration of a powdered medicament by inhalation, the systemcomprising a container containing a unit dose of medicament in powderform, the container having at least one dispensing aperture, and adevice having a chamber adapted to receive said container, the devicefurther comprising air inlet means by which air may be drawn into thechamber and means by which air and entrained medicament may be drawn outof the chamber, wherein the system is arranged such that the container,in use, is stationary within the chamber.

The system according to the invention is advantageous primarily in thatthe medicament container empties without undergoing movement. As aresult, the noise generated in use is low. Because the container doesnot need to undergo motion brought about by the airflow in the device,the required airflow in the device is relatively low, leading to greaterease of use, eg by users with impaired lung function.

It will be appreciated that inhalation of the medicament may be oralinhalation, or nasal inhalation. In either case, the device may beappropriately formed for the desired mode of administration. Forexample, the device may be formed with a mouthpiece or the like tofacilitate inhalation. Likewise, for nasal inhalation, the device may beformed with an extension adapted to be offered up to, or inserted into,the user's nostril.

The device may be configured for single or repeated use. In either case,the device is preferably provided with means for storing the container,whilst sealing the at least one aperture, means for introducing thecontainer into the chamber, and means for holding the containerstationary within the chamber.

It will be appreciated that the system according to the invention maycomprise a device and a single container, or a device and a plurality ofcontainers. In the latter case, the plurality of containers may eachcontain the same medicament, or the containers may contain doses of twoor more different medicaments, for simultaneous or sequentialadministration.

Where the system comprises a plurality of containers, those containersmay be held in a magazine or cartridge that is coupled with the deviceto enable each container to be introduced sequentially into the chamber.For instance, the cartridge may take the form of a rotatable disk,suitable mechanical means being provided for indexing of the cartridgeso as to bring the containers into registration with the chamber.

Preferably, the means for storing the container and introducing thecontainer into the chamber take the form of an enclosure of deformablematerial arranged such that manual pressure introduces the containerinto the chamber.

According to another, more specific, aspect of the invention, there isprovided a system for the administration of a powdered medicament byinhalation, the system comprising a container containing a unit dose ofmedicament in powder form, the container having at least one dispensingaperture, and a device having a chamber adapted to receive saidcontainer, the device further comprising air inlet means by which airmay be drawn into the chamber and means by which air and entrainedmedicament may be drawn out of the chamber, wherein a part of the wallof the chamber is formed as a deformable enclosure within which thecontainer is received such that the at least one dispensing aperture issealed and from which the container can be introduced into the chamberby pressure applied to the external surface of the deformable enclosure,the system being arranged such that when the container is introducedinto the chamber, the container is held stationary.

The container may be held stationary within the chamber by any suitablemeans. For instance, the container may be physically attached to theenclosure, such that when the enclosure is deformed and the containerthereby introduced into the chamber the attachment of the container tothe enclosure prevents movement of the container within the chamber.Alternatively, the container and/or the chamber may be provided withformations that are effective in holding the container in a stationaryposition once the container has been introduced into the chamber. Forinstance, the chamber may be provided with a recess in which thecontainer is received when introduced into the chamber. Alternatively,the wall of the chamber that faces the enclosure may be provided withone or more projections that engage the container when the container isintroduced into the chamber. In a further alternative, the container maybe provided with one or more locating formations that engage withcorresponding formations provided in the chamber. For instance, thecontainer may be provided with a projecting lug that engages in a recessor opening formed in the wall of the chamber opposite to the enclosure.In a further alternative, there may be no physical attachment betweenthe container and the chamber, but the dimensions of the container maybe such that, when introduced into the chamber from the enclosure, it issimply captivated between opposing parts of the chamber, eg the base ofthe chamber and the periphery of the enclosure.

Where the container is physically attached to the enclosure, this may beby means of a projection formed on the container that extends through anopening in the enclosure. Such a projection may take the form of a stud,preferably formed integrally with the container, that projects throughan opening in the enclosure and has an enlarged upper portion.Alternatively, the container may be bonded to the enclosure. Suchbonding may be brought about by the application of heat and/or pressure,or alternatively by the use of adhesive.

In the case of a device intended for single use and then disposal, themeans by which air and entrained medicament are drawn out of the chambermay simply comprise one or more apertures formed in a wall of thechamber. Preferably, these apertures and the air inlet means are sealedprior to use. Such a seal is most conveniently achieved by the provisionof a removable sealing membrane, eg in the form of a laminated plasticssheet which is fixed in place by a suitable adhesive. The sealingmembrane is preferably provided with a projecting portion or tab bywhich it can be grasped for ease of removal.

In the case of a device intended for repeated use, the enclosure andcontainer may form a medicament package which may be attached to, andremoved from, the delivery device. In such a case the medicament packagepreferably comprises a rigid support to which the enclosure is bonded,and the device is preferably provided with receiving means with whichthe rigid support can be engaged. Such receiving means may take the formof grooved formations with which the rigid support can be engaged. Thereceiving means are preferably provided adjacent an opening in thedevice such that engagement of the medicament package with the receivingmeans closes the opening.

The chamber is preferably circular in form. In some embodiments, the airinlet means are preferably arranged such that air enters the chambersubstantially tangentially so as to facilitate the emptying of thecontainer. There may be provided a plurality of air inlets, which may,but do not necessarily, open into the chamber at substantiallyequiangularly spaced positions.

The medicament container may have any shape. However, the container ispreferably cylindrical or substantially cylindrical. In someembodiments, the diameter of the cylinder is typically comparable to orgreater than its depth. For example, the depth of the cylinder may be nomore than 1.5 times the diameter of the cylinder, and more preferably isequal to or less than the diameter. The container thus preferably hasthe form of a drum.

The medicament container is preferably provided with a plurality ofdispensing apertures. In the case of a cylindrical container, thedispensing apertures are preferably disposed equiangularly around thecylindrical periphery of the container.

The device may be manufactured from materials conventionally utilised ininhalation drug delivery devices. For reasons of cost and manufacturingconvenience, the device is most preferably manufactured by injectionmoulding in plastics material. Examples of suitable plastics materialsinclude polycarbonate, polypropylene and polyethylene. Metals may alsobe used to form all or part of the device. Examples of suitable metalsinclude aluminium and stainless steel. The device may be formed as asingle injection-moulded component, or it may comprise a plurality ofcomponents that are subsequently bonded or otherwise connected together.

The enclosure is most preferably formed in deformable plastics material.The enclosure may be formed in the same material as the device, thenecessary deformability being created if necessary by the use ofmaterial of reduced thickness. Alternatively, the enclosure may beformed in elastomeric material, most preferably a medical gradethermoplastic rubber. In such a case, the enclosure may be formed,together with the rest of the device (or the part of the device to whichthe enclosure is attached), or with the rigid support that together withthe enclosure makes up a medicament package, by a two-shot mouldingoperation in which a first moulding is made in a relatively rigidplastics material and the elastomeric material is then moulded onto thefirst moulding.

The medicament container is preferably of a material which issubstantially impermeable to moisture. The container is preferably ofplastics material, most preferably polypropylene. The container maycomprise two or more cooperating components that together define thecontainer. Most preferably, the container is formed in two parts thatfit together with a snap-fit or the like, one or both parts havingformations that define the at least one dispensing aperture at thejunction of the two parts. The two or more cooperating parts arepreferably manufactured by injection moulding. As an alternative to theuse of plastics materials, one or more parts of the container may beformed in metal, eg by pressing from a suitable sheet of metal. Metalsthat may be used include aluminium.

The invention will now be described in greater detail, by way ofillustration only, with reference to the accompanying drawings, in which

FIG. 1 is a plan view of a first embodiment of a powdered medicamentinhaler according to the invention;

FIG. 2 is a side view of a medicament container that forms part of theinhaler of FIG. 1;

FIG. 3 is a sectional view along line III-III of FIG. 1;

FIG. 4 is a sectional view along line IV-IV of FIG. 3;

FIG. 5 is a sectional view, along line III-III of FIG. 1, of the inhalerin use;

FIG. 6 is a plan view of a second embodiment of a powdered medicamentinhaler according to the invention;

FIG. 7 is a sectional view along line VII-VII of FIG. 6;

FIG. 8 is a side view of a medicament package according to theinvention;

FIG. 9 is a view similar to that of FIG. 7, of the inhaler engaged witha medicament package;

FIG. 10 is a view similar to that of FIG. 9, of the inhaler in use;

FIG. 11 is a front view of a third embodiment of a powdered medicamentinhaler according to the invention;

FIG. 12 is a rear view of the inhaler of FIG. 11;

FIG. 13 is a sectional view along the line XIII-XIII of FIG. 11;

FIG. 14 is a view similar to that of FIG. 13 of the inhaler during use;and

FIG. 15 is a plan view of a further embodiment of an inhaler accordingto the invention, adapted for nasal inhalation.

Referring first to FIGS. 1 and 2, a first embodiment of a medicamentinhaler according to the invention is generally designated 10. Theinhaler 10 comprises a main body 18, an enclosure 14 and a medicamentcontainer 20. The main body 18 and the medicament container 20 are bothmoulded in plastics material, whilst the enclosure 14 is of elastomericmaterial. In the drawings, the main body 18 is shown as a unitarycomponent, but in practice it may be necessary or desirable for the mainbody 18 to be formed as two or more separate components that areassembled together in a subsequent fabrication step.

Referring to FIG. 2, the container 20 is formed from two interlockingcomponents 20 a and 20 b, each of which is injection-moulded in plasticsmaterial, such that the container 20 has a cylindrical lower part and anupper part of generally domed or conical shape. The abutting edges ofthe two components 20 a, 20 b are formed so as to define a series ofequiangularly spaced apertures 21. At the apex of the upper part of thecontainer, the container 20 is formed with an integral stud 22 having anenlarged upper portion.

Referring to FIGS. 1, 3 and 4, the main body 18 comprises a mouthpiece11, a passageway 16, a chamber 19, conduits 12 a, 13 a and air inlets12, 13. The mouthpiece is a generally elliptical opening in one end ofthe main body 18. The passageway extends from the mouthpiece 11 andthrough the lower part of the main body 18. The chamber 19 iscylindrical in shape and is positioned above the passageway 16. Thechamber 19 communicates with the passageway 16 by means of a series ofopenings which make up a generally circular grid 15 in the centre of thebase of the chamber 19, as shown in FIG. 4.

There are two front air inlets 12 and two rear air inlets 13 whichconnect the wall of the chamber 19 and the exterior of the inhaler 10 bymeans of respective conduits 12 a, 13 a, as shown in FIG. 4. Theconduits 12 a, 13 a are aligned substantially tangentially to the wallof the chamber 19 and connect to the chamber 19 at equiangularly spacedlocations.

Referring now to FIG. 3, the upper wall of the chamber 19 includes acircular aperture 17. The interior wall of the circular aperture 17 isbonded to the enclosure 14, the enclosure 14 extending above the chamber19. The enclosure 14 is of similar shape to the container 20 save thatthe enclosure 14 has an open lower end and a circular aperture at itsapex. The enclosure 14 is dimensioned such that the container 20 isclosely received within the enclosure 14 with an interference fit andthe stud 22 is pressed through the aperture of the enclosure 14, therebyholding the container 20 within the enclosure 14. The aperture of theenclosure 14 is dimensioned such that the lower portion of the stud fitsclosely within the aperture of the enclosure 14. The inhaler 10 is shownin FIG. 3 prior to use, with the medicament sealed within the container10.

When the patient is ready to use the inhaler 10, the patient appliesdownward finger pressure on the enclosure 14 such that the enclosure 14is turned inside out and extends partially into the chamber 19. The stud22 projecting through the aperture of the enclosure 14 remains in thisposition thereby holding the container 20 in the centre of the chamber19, as shown in FIG. 5.

The patient then places the mouthpiece 11 to their mouth and inhales.Air is drawn through the air inlets 12, 13, along the conduits 12 a, 13a and substantially tangentially into the chamber 19. The airstreampasses through the grid 15 and along the passageway 16 to the patientsmouth. The stream of air entering the chamber 19 causes the medicamentto be dispensed from within the medicament container 20, through theapertures 21 of the container 20, into the chamber 19. The medicament isentrained in the airstream which passes out of the chamber 19 throughthe grid and is inhaled by the patient. The first embodiment 10 is asingle-use delivery device and would be discarded after use.

Turning now to FIGS. 6, 7, 8 and 9, a second embodiment of a medicamentinhaler according to the invention is generally designated 50. Thesecond embodiment 50 is similar to the first embodiment 10 save that themedicament container 61 and the enclosure 62 together form a separatecomponent from the inhaler 50.

The enclosure 62 and the medicament container 61, for use with thesecond embodiment of the inhaler 50, are identical to the enclosure 14and container 20 of the first embodiment of inhaler 10. The enclosure 62and container 61, together with a support ring 63, form a medicamentpackage 60, as shown in FIG. 8. The container 61 is closely receivedwith an interference fit, as in the first embodiment, within theenclosure 62, with the stud 65 of the container 61 projecting out of theaperture of the enclosure 62. The support ring 63 comprises an annularplate and a vertically orientated upper and lower skirt on the inneredge of the annular plate. The support ring 63 fits closely around, andis bonded to, the outside of the cylindrical lower section of theenclosure 62.

The inhaler 50 is similar to the main body 18 of the first embodiment10, save that the enclosure 62 is not bonded to the circular aperture 52in the upper end of the chamber 56 The aperture 52 is provided with aperipheral groove 53 and an upper section of enlarged diameter, suchthat the support ring 63 of the medicament package 60 may be snap fittedfrom above into the groove 53 within the aperture 52. The upper surfaceof the inhaler 50 is provided with a rectangular depression 51 whichextends from the aperture 52 and is dimensioned to accommodate the padof the patient's thumb.

In order to load the inhaler 50, the medicament package 60 issnap-fitted, as described above, into the aperture 52, as shown in FIG.10. The method of use is thenceforth identical to the method of use forthe first embodiment 10. After use, however, the patient places theirthumb in the depression 51 and exerts an upward pressure on the supportring 63 of the medicament package 60, thereby releasing the medicamentpackage from the aperture 52. The inhaler 50 may subsequently bereloaded with another medicament package 60.

Turning now to FIGS. 11, 12 and 13, a third embodiment of a medicamentinhaler according to the invention is generally designated 100. Theinhaler 100 comprises a flat plastics rectangular base 104 heat-sealedto a formed plastics front portion 102, and a removable laminate coversheet 106 glued to the outer surface of the front portion 102.

The front portion 102 defines a circular chamber 110 having a passageway112 extending radially from the side wall of the chamber 110 along thelongitudinal axis of the front portion 102. The passageway 112 has anair inlet 113 at the end of the passageway 112 remote from, but in fluidcommunication with, the chamber 110.

The base 104 includes a deformable enclosure 105 that accommodates amedicament container 120 with a close fit. The medicament container 120contains a unit dose of medicament and is similar to the medicamentcontainers 20 and 61 of the first and second embodiments save thatmedicament container 120 is generally cylindrical in form and does nothave a stud corresponding to the studs 22,65 of the first and secondembodiments. The deformable enclosure 105 is formed so as to sealapertures formed in the side of the container 120 and hold the container120 in a position immediately adjacent the chamber 110.

The circular front wall of the chamber 110 includes an array ofapertures 111. The front wall of the chamber 110 is adapted so as to bepressed to a patient's lips so that it may act as a mouthpiece. Whencover sheet 106 is attached to the inhaler 100, prior to use, apertures111 and air inlet 113 are sealed.

In order to use the inhaler 100, a patient simply pulls on a tab portion107 of the cover sheet 106. The cover sheet 106 consequently peels awayfrom the surface of the front portion 102 to open apertures 111 and airinlet 113. The deformable enclosure 105 is then depressed, and thereforedeformed, using finger pressure so that the medicament container 120 isintroduced into the chamber 110, as shown in FIG. 14. The depth of thechamber 110 is substantially the same as the depth of the container 120and this, together with the resilience of the material from which thebase 104 and front portion 102 are formed, results in the container 120being held stationary within the chamber 110.

The mouthpiece is then offered up to the patient's lips, whereuponinhalation through the apertures 111 causes air to be drawn into airinlet 113, along passageway 112 and into chamber 110 where the unit doseof medicament contained within the medicament container 120 is entrainedby the airstream and inhaled, through the apertures 111, by the patient.

Finally, FIG. 15 shows a further embodiment of an inhaler 150 accordingto the invention. This embodiment 150 is broadly similar in function tothat of FIGS. 6 and 7, in that it comprises a main body 151 with aremovable medicament package comprising a flexible, dome-shapedenclosure 152 bonded to a rigid support ring 153. The ring 153 is slidbeneath retaining formations 154 that are formed integrally with themain body 151 in order to position the enclosure 152 above the chamberof the device (not visible). Air inlets 155 communicate with the chamberin the same manner as for the previously-described embodiments. Thisembodiment differs from those previously-described embodiments in thatthe outlet 156 through which air, and entrained medicament, is withdrawnfrom the device is relatively narrow and is shaped and dimensioned forinsertion into the user's nostril. This embodiment is therefore suitablefor nasal inhalation.

1. A system for the administration of a powdered medicament byinhalation, the system comprising a container containing a unit dose ofmedicament in powder form, the container having at least one dispensingaperture, and a device having a chamber adapted to receive saidcontainer, the device further comprising air inlet means by which airmay be drawn into the chamber and means by which air and entrainedmedicament may be drawn out of the chamber, wherein a part of the wallof the chamber is formed as a deformable enclosure within which thecontainer is received such that the at least one dispensing aperture issealed and from which the container can be introduced into the chamberby pressure applied to the external surface of the deformable enclosure,the system being arranged such that when the container is introducedinto the chamber the container is held stationary.
 2. A system asclaimed in claim 1, wherein the system comprises a device and aplurality of medicament containers.
 3. A system as claimed in claim 1,wherein the container is physically attached to the enclosure.
 4. Asystem as claimed in claim 3, wherein the container is formed with aprojection that extends through an opening in the enclosure.
 5. A systemas claimed in claim 3, wherein the container is bonded to the enclosure.6. A system as claimed in claim 1, wherein the container and/or thechamber are provided with formations that are effective in holding thecontainer in a stationary position once the container has beenintroduced into the chamber.
 7. A system as claimed in claim 1, whereinthe container is held stationary by virtue of being captivated betweenopposing parts of the chamber after being released from the enclosure.8. A system as claimed in claim 1, wherein the means by which air andentrained medicament are withdrawn from the chamber comprises one ormore apertures formed in a wall of the chamber.
 9. A system as claimedin claim 8, wherein the apertures and the air inlet means are sealedprior to use by a removable sealing membrane.
 10. A system as claimed inclaim 1, wherein the enclosure and container from a medicament packagewhich may be removed from the delivery device.
 11. A system as claimedin claim 10, wherein the medicament package comprises a rigid support towhich the enclosure is bonded, and the device is provided with receivingmeans with which the rigid support can be engaged.
 12. A system asclaimed in claim 1, wherein the chamber is circular in form.
 13. Asystem as claimed in claim 12, wherein the air inlet means are arrangedsuch that air enters the chamber substantially tangentially so as tofacilitate the emptying of the container.
 14. A system as claimed inclaim 1, wherein the device is provided with a plurality of air inletsopening into the chamber at substantially equiangularly spacedpositions.
 15. A system as claimed in claim 1, wherein the medicamentcontainer is cylindrical.
 16. A system as claimed in claim 15, whereinthe diameter of the cylinder is comparable to or greater than its depth.17. A system as claimed in claim 16, wherein the depth of the cylinderis equal to or less than its diameter.
 18. A system as claimed in claim1, wherein the medicament container is provided with a plurality ofdispensing apertures.
 19. A system as claimed in claim 1, wherein theenclosure is of elastomeric material.
 20. A system as claimed in claim1, wherein the medicament container is of plastics material.